Case of metastatic clear cell odontogenic carcinoma with response to chemoimmunotherapy.

Our patient initially presented with 6 months of left jaw pain and gingival bleeding, leading to the discovery of a radiolucent left maxillary mass on dental evaluation. A biopsy confirmed clear cell odontogenic carcinoma, and the patient was treated with definitive surgery and radiation for localised disease. Unfortunately, the patient was found to have pulmonary metastases 3 months after initial management and was subsequently treated with a combination of cytotoxic chemotherapy and immunotherapy with a partial response. To our knowledge, this is the first case demonstrating the successful use of chemoimmunotherapy in metastatic clear cell odontogenic carcinoma.

A scoping review of antimicrobial resistance in the Australian dairy cattle industry.

INTRODUCTION: Quantification of antimicrobial resistance (AMR) is beneficial to inform policies and direct prudent antimicrobial use. AIM: This study aimed to assess the current published evidence of AMR from passive and active ad hoc surveillance activities within the Australian dairy cattle industry. METHODS: Following a scoping review framework 373 articles published before January 2023 were retrieved using the keyword search function from two online databases (PubMed® and Web of Science™ Core Collection). The duplicate articles were removed and the title, abstract, and full text of the remaining articles were reviewed following the study objectives and inclusion criteria (location, subject/theme, and data). Data from the remaining articles were extracted, summarised, interpreted and the study quality assessed using the Grades of Recommendations, Assessment, Development, and Evaluation guidelines. RESULTS: A total of 29 articles dating from the 1960 s until 2022 were identified to meet the study criteria (passive: n = 15; active: n = 14). Study characteristics such as sampling type, sampling method, and AMR assessment were all common characteristics from both passive and active surveillance articles, being milk samples, individual sampling, and phenotypic assessment respectively. Passive surveillance articles had a wider range in both the type of bacteria and the number of antimicrobials investigated, while active surveillance articles included a higher number of bacterial isolates and sampling from healthy populations. There was an overall low level of clinical AMR across all articles. Higher prevalence of non-wildtype Escherichia coli, Salmonella spp., and Staphylococcus spp., although limited in data, was suggested for commonly used Australian veterinary antimicrobials for these bacteria. The prevalence of phenotypic AMR varied due to the health and age status of the sampled animals. The articles reviewed in this study suggest the prevalence of AMR genes was higher for commonly used antimicrobials, although genes were not always related to the phenotypic AMR profile. CONCLUSIONS: Published evidence of AMR in the Australian dairy cattle industry is limited as demonstrated by only 29 articles included in this review following selection criteria screening. However, collectively these articles provide insight on industry AMR prevalence. For example, the suggestion of non-wildtype bacteria within the Australian dairy cattle indicating a risk of emerging or increasing industry AMR. Therefore, further surveillance is required to monitor the development of future AMR risk within the industry. Additionally, evidence suggesting that animals varying in health and age differ in prevalence of AMR imply a requirement for further research into animal population demographics to reduce potential bias in data collated in both national and global surveillance activities.

Physics-Informed Deep Learning for Muscle Force Prediction With Unlabeled sEMG Signals.

Computational biomechanical analysis plays a pivotal role in understanding and improving human movements and physical functions. Although physics-based modeling methods can interpret the dynamic interaction between the neural drive to muscle dynamics and joint kinematics, they suffer from high computational latency. In recent years, data-driven methods have emerged as a promising alternative due to their fast execution speed, but label information is still required during training, which is not easy to acquire in practice. To tackle these issues, this paper presents a novel physics-informed deep learning method to predict muscle forces without any label information during model training. In addition, the proposed method could also identify personalized muscle-tendon parameters. To achieve this, the Hill muscle model-based forward dynamics is embedded into the deep neural network as the additional loss to further regulate the behavior of the deep neural network. Experimental validations on the wrist joint from six healthy subjects are performed, and a fully connected neural network (FNN) is selected to implement the proposed method. The predicted results of muscle forces show comparable or even lower root mean square error (RMSE) and higher coefficient of determination compared with baseline methods, which have to use the labeled surface electromyography (sEMG) signals, and it can also identify muscle-tendon parameters accurately, demonstrating the effectiveness of the proposed physics-informed deep learning method.

Tuning the potency and selectivity of ImmTAC molecules by affinity modulation.

T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T-cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against cancer (ImmTAC) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the redirected T-cell response. This class of bispecifics binds specific target peptides presented by human leukocyte antigen on the cell surface via an affinity-enhanced T-cell receptor and can redirect T-cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T-cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimizing the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proofreading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark state. These findings have important implications for the design of anti-CD3-based bispecifics with optimal biophysical parameters for both activity and specificity.

The Brain Health Diplomat's Toolkit: supporting brain health diplomacy leaders in Latin America and the Caribbean.

Maintaining and improving brain health, one of the most critical global challenges of this century, necessitates innovative, interdisciplinary, and collaborative strategies to address the growing challenges in Latin America and the Caribbean. This paper introduces Brain Health Diplomacy (BHD) as a pioneering approach to bridge disciplinary and geographic boundaries and mobilize resources to promote equitable brain health outcomes in the region. Our framework provides a toolkit for emerging brain health leaders, equipping them with essential concepts and practical resources to apply in their professional work and collaborations. By providing case studies, we highlight the importance of culturally sensitive, region-specific interventions to address unique needs of vulnerable populations. By encouraging dialogue, ideation, and cross-sector discussions, we aspire to develop new research, policy, and programmatic avenues. The novel BHD approach has the potential to revolutionize brain health across the region and beyond, ultimately contributing to a more equitable global cognitive health landscape.

Nonfamilial Bilateral Synchronous Renal Cell Carcinoma with Discordant Histology with Eventual Complete Response to Dual Immunotherapy.

Bilateral synchronous renal cell carcinoma (RCC) is rare, especially in sporadic rather than familial cases. While immunotherapy has improved prognosis, RCC remains a diagnosis with significant morbidity and mortality, particularly pronounced in patients with sarcomatoid RCC (sRCC). We describe a case of a patient with bilateral, synchronous, nonfamilial RCC, with and without sarcomatoid features and differing genetic markers, who demonstrated a pathologic response after neoadjuvant nivolumab and ipilimumab. The patient then had radical left nephrectomy and partial right nephrectomy followed by adjuvant nivolumab and cabozantinib, after which the patient had no evidence of disease. Our patient's illustrative case shows the potential therapeutic value of immunotherapy even in sRCC, the disease's most aggressive clinical subtype.

Elevated emotion network connectivity is associated with fluctuations in depression.

Elevated emotion network connectivity is thought to leave people vulnerable to become and stay depressed. The mechanism through which this arises is however unclear. Here, we test the idea that the connectivity of emotion networks is associated with more extreme fluctuations in depression over time, rather than necessarily more severe depression. We gathered data from two independent samples of N = 155 paid students and N = 194 citizen scientists who rated their positive and negative emotions on a smartphone app twice a day and completed a weekly depression questionnaire for 8 wk. We constructed thousands of personalized emotion networks for each participant and tested whether connectivity was associated with severity of depression or its variance over 8 wk. Network connectivity was positively associated with baseline depression severity in citizen scientists, but not paid students. In contrast, 8-wk variance of depression was correlated with network connectivity in both samples. When controlling for depression variance, the association between connectivity and baseline depression severity in citizen scientists was no longer significant. We replicated these findings in an independent community sample (N = 519). We conclude that elevated network connectivity is associated with greater variability in depression symptoms. This variability only translates into increased severity in samples where depression is on average low and positively skewed, causing mean and variance to be more strongly correlated. These findings, although correlational, suggest that while emotional network connectivity could predispose individuals to severe depression, it could also be leveraged to bring about therapeutic improvements.

A Rare Case of Takayasu Arteritis Presenting as Pericarditis with Effusion.

Takayasu arteritis (TAK) is a rare large-vessel vasculitis that is seen primarily in young females of Asian descent and is infrequently diagnosed in the United States. Pericardial effusion with or without pericarditis as a presenting feature of TAK is rare, with only about five percent of cases of pericarditis attributable to any autoimmune etiology. We present a case of a 22-year-old Caucasian woman who presented with a large, symptomatic pericardial effusion of unclear etiology, who after extensive laboratory workup and imaging to include whole-body positron emission tomography (PET) was diagnosed with TAK. In our patient, the use of whole-body PET showing characteristic hypermetabolism within the aortic arch helped secure our diagnosis while avoiding the need for pericardiocentesis. The patient had rapid symptomatic and radiographic improvement with the use of high-dose oral steroids in addition to colchicine and ibuprofen for her pericarditis and associated pericardial effusion. At follow-up just 1 week after initiation of steroids, only trace effusion was identified on transthoracic echocardiogram.

A participatory approach to understand the attitudes and perceptions towards priority endemic cattle diseases among dairy farmers and animal health experts in Henan province, China.

The dairy industry is threatened by a variety of endemic diseases and emerging diseases, and various control programs have been initiated in China. The increased application of evidence to policymaking can help improve the efficiency of disease control programs; however, the relevant research literature is currently lacking. The objective of this study was to gain an in-depth understanding of the attitudes and perceptions towards priority endemic diseases among dairy farmers and animal health experts by taking Henan province of China as the example and using semi-structured interviews and focus group discussions, respectively. This study involved 24 farmers and 27 animal health experts from December 2019 to January 2021. The diseases considered by farmers to be of significance to their animals are different from those considered priorities by the participating experts and the government list. From the perspective of the individual farmers, the effects of zoonotic disease risks such as bovine brucellosis and tuberculosis appear to be less pronounced than "visible" losses at the farm level, contrary to the opinion of experts. Participating experts believed that poor on-farm biosecurity measures posed challenges to the control and eradication of priority endemic diseases; however, there are gaps in farmers' understanding of biosecurity principles, and low motivations to take such disease prevention measures. Several other challenges to the control and eradication of priority endemic diseases also emerged in the data, including the lack of diagnostic tools applicable in the field as well as differential diagnostic tools to differentiate natural infection from vaccination, lack of effective and commercially available vaccines against single or multiple pathogen(s) or new genotypes/serotypes, weak early warning and information networks and insufficient economic compensation. A holistic understanding of people's perceptions of disease control would facilitate the implementation of inclusive and engaging disease control strategies, thereby increasing the efficiency of disease control.

An Accurate Millimeter-Wave Imaging Algorithm for Close-Range Monostatic System.

An efficient and more accurate millimeter-wave imaging algorithm, applied to a close-range monostatic personnel screening system, with consideration of dual path propagation loss, is presented in this paper. The algorithm is developed in accordance with a more rigorous physical model for the monostatic system. The physical model treats incident waves and scattered waves as spherical waves with a more rigorous amplitude term as per electromagnetic theory. As a result, the proposed method can achieve a better focusing effect for multiple targets in different range planes. Since the mathematical methods in classical algorithms, such as spherical wave decomposition and Weyl identity, cannot handle the corresponding mathematical model, the proposed algorithm is derived through the method of stationary phase (MSP). The algorithm has been validated by numerical simulations and laboratory experiments. Good performance in terms of computational efficiency and accuracy has been observed. The synthetic reconstruction results show that the proposed algorithm has significant advantages compared with the classical algorithms, and the reconstruction by using full-wave data generated by FEKO further verifies the validity of the proposed algorithm. Finally, the proposed algorithm performs as expected over real data acquired by our laboratory prototype.

Recent Therapeutic Advances in Pituitary Carcinoma.

Pituitary carcinoma (PC) is a rare, aggressive malignancy that comprises 0.1-0.2% of all pituitary tumors. PC is defined anatomically as a pituitary tumor that metastasizes outside the primary intrasellar location as noncontiguous lesions in the central nervous system or as metastases to other organs. Similar to pituitary adenoma, PC originates from various cell types of the pituitary gland and can be functioning or nonfunctioning, with the former constituting the majority of the cases. Compression of intricate skull-based structures, excessive hormonal secretion, impaired pituitary function from therapy, and systemic metastases lead to debilitating symptoms and a poor survival outcome in most cases. PC frequently recurs despite multimodality treatments, including surgical resection, radiotherapy, and biochemical and cytotoxic treatments. There is an unmet need to better understand the pathogenesis and molecular characterization of PC to improve therapeutic strategies. As our understanding of the role of signaling pathways in the tumorigenesis of and malignant transformation of PC evolves, efforts have focused on targeted therapy. In addition, recent advances in the use of immune checkpoint inhibitors to treat various solid cancers have led to an interest in exploring the role of immunotherapy for the treatment of aggressive refractory pituitary tumors. Here, we review our current understanding of the pathogenesis, molecular characterization, and treatment of PC. Particular attention is given to emerging treatment options, including targeted therapy, immunotherapy, and peptide receptor radionuclide therapy.

Post-lumbar surgery prescription variation and opioid-related outcomes in a large US healthcare system: an observational study.

BACKGROUND CONTEXT: Spinal decompression and fusion procedures are one of the most common procedures performed in the United States (US) and remain associated with high postsurgical opioid burden. Despite guidelines emphasizing nonopioid pharmacotherapy strategies for postsurgical pain management, prescribing practices are likely variable and guideline-incongruent. PURPOSE: The purpose of this study was to characterize patient-, care-, and system-level factors associated with opioid, nonopioid pain medication, and benzodiazepine prescribing variation in the US Military Health System (MHS). STUDY DESIGN/SETTING: Retrospective study analyzing medical records from the US MHS Data Repository. PATIENT SAMPLE: Adult patients (N=6,625) undergoing lumbar decompression and spinal fusion procedures from 2016 to 2021 in the MHS enrolled in TRICARE at least a year prior to their procedure and had at least one encounter beyond the 90-day postprocedure period, without recent trauma, malignancy, cauda equina syndrome, and co-occurring procedures. OUTCOME MEASURES: Patient-, care-, and system-level factors influencing outcomes of discharge morphine equivalent dose (MED), 30-day opioid refill, and persistent opioid use (POU). POU was defined as dispensing of opioid prescriptions monthly for the first 3 months after surgery and then at least once between 90 and 180 days after surgery. METHODS: (Generalized) linear mixed models evaluated multilevel factors associated with discharge MED, opioid refill, and POU. RESULTS: The median discharge MED was 375 mg (IQR 225, 580) and days' supply was 7 days (IQR 4, 10); 36% received an opioid refill and 5%, overall, met criteria for POU. Discharge MED was associated with fusion procedures (+151-198 mg), multilevel procedures (+26 mg), policy release (-184 mg), opioid naïvty (-31 mg), race (Black -21 mg, another race and ethnicity -47 mg), benzodiazepine receipt (+100 mg), opioid-only medications (+86 mg), gabapentinoid receipt (-20 mg), and nonopioid pain medications receipt (-60 mg). Longer symptom duration, fusion procedures, beneficiary category, mental healthcare, nicotine dependence, benzodiazepine receipt, and opioid naivety were associated with both opioid refill and POU. Multilevel procedures, elevated comorbidity score, policy period, antidepressant receipt, and gabapentinoid receipt, and presurgical physical therapy were also associated with opioid refill. POU increased with increasing discharge MED. CONCLUSIONS: Significant variation in discharge prescribing practices require systems-level, evidence-based intervention.

Epidemiological Survey and Risk Factor Analysis of 14 Potential Pathogens in Golden Snub-Nosed Monkeys at Shennongjia National Nature Reserve, China.

Golden snub-nosed monkeys (Rhinopithecus roxellanae) belong to Class A, the highest level of endangered primate species. Exploring the infection status of potential pathogens in golden snub-nosed monkeys is important for controlling associated diseases and protecting this species. The objective of this study was to investigate the seroprevalence for a number of potential pathogens and the prevalence of fecal adenovirus and rotavirus. A total of 283 fecal samples were collected from 100 golden snub-nosed monkeys in December 2014, June 2015, and January 2016; 26 blood samples were collected from 26 monkeys in June 2014, June 2015, January 2016 and November 2016 at Shennongjia National Reserve in Hubei, China. The infection of 11 potential viral diseases was examined serologically using an Indirect Enzyme-linked Immunosorbent Assay (iELISA) and Dot Immunobinding Assays (DIA), while the whole blood IFN-γ in vitro release assay was used to test tuberculosis (TB). In addition, fecal Adenovirus and Rotavirus were detected using Polymerase Chain Reaction (PCR). As a result, the Macacine herpesvirus-1 (MaHV-1), Golden snub-nosed monkey cytomegalovirus (GsmCMV), Simian foamy virus (SFV) and Hepatitis A virus (HAV) were detected with the seroprevalence of 57.7% (95% CI: 36.9, 76.6), 38.5% (95% CI: 20.2, 59.4), 26.9% (95% CI: 11.6, 47.8), and 7.7% (95% CI: 0.0, 84.2), respectively. Two fecal samples tested positive for Adenovirus (ADV) by PCR, with a prevalence of 0.7% (95% CI: 0.2, 2.5), and further, the amplification products were sequenced. Phylogenetic analysis revealed that they belonged to the HADV-G group. However, other pathogens, such as Coxsackievirus (CV), Measles virus (MeV), Rotavirus (RV), Simian immunodeficiency virus (SIV), Simian type D retroviruses (SRV), Simian-T-cell lymphotropic virus type 1 (STLV-1), Simian varicella virus (SVV), Simian virus 40 (SV40) and Mycobacterium tuberculosis complex (TB) were negative in all samples. In addition, a risk factor analysis indicated that the seroprevalence of MaHV-1 infection was significantly associated with old age (≥4 years). These results have important implications for understanding the health status and conservation of the endangered golden snub-nosed monkey population at Shennongjia Nature Reserve.

Prevalence, distribution, and risk factors of bovine tuberculosis in dairy cattle in central China.

Bovine tuberculosis (bTB) is one of the priority epidemic diseases in dairy cattle in China. Continuous surveillance and evaluation of the control programs will help on improving the efficiency of bTB control policy. We designed this study to investigate both animal and herd level prevalence of bTB, as well as to determine the associated factors in dairy farms in Henan and Hubei provinces. A cross-sectional study was conducted from May 2019 to September 2020 in central China (Henan and Hubei provinces). We sampled 40 herds in Henan and six herds in Hubei via stratified systematic sampling and administrated a questionnaire consisting of 35 factors. A total of 4900 whole blood samples were collected from 46 farms, including 545 calves < six months old and 4355 cows ≥ six months old. This study demonstrated a high animal-(18.65%, 95% CI: 17.6-19.8) and herd-level (93.48%, 95%CI: 82.1-98.6) prevalence of bTB in dairy farms in central China. The Least Absolute Shrinkage and Selection Operator (LASSO) and negative binomial regression models showed that herd positivity was associated with the practice of introducing new animals (RR = 1.7, 95%CI: 1.0-3.0, p = 0.042), and changing the disinfectant water in the wheel bath at the farm entrance every three days or less (RR = 0.4, 95%CI: 0.2-0.8, p = 0.005) which reduced the odds of herd positivity. In addition, the result illustrated that testing cows with a higher age group (≥ 60 months old) (OR=1.57, 95%CI: 1.14-2.17, p = 0.006) and within the early stage of lactation (DIM=60-120 days, OR=1.85, 95%CI: 1.19-2.88, p = 0.006) and the later stage of lactation (DIM≥301 days, OR=2.14, 95%CI: 1.30-3.52, p = 0.003) could maximize the odds of detecting seropositive animals. Our results have plenty of benefit to improve bTB surveillance strategies in China and elsewhere in the world. The LASSO and the negative binomial regression models were recommended when dealing with high herd-level prevalence and high dimensional data in questionnaire-based risk studies.

Individual and Herd-Level Seroprevalence in Association with Potential Risk Factors of Japanese Encephalitis in Pigs Collected from Urban, Periurban, and Rural Areas of Bali, Indonesia.

A study to assess the seroprevalence antibodies against JEV in pigs in Denpasar, Badung, and Karangasem as the representatives of urban, periurban, and rural areas in the province of Bali was conducted. Sampled pigs' blood was collected and their sera were tested for antibody detection using commercial IgG ELISA. A standard questionnaire was used to interview the pig owners or farmers to identify the determinants associated with the seropositivity of the antibodies. Overall, 96.6% (95% CI: 94.5-98.1) of 443 pig sera in individual animal-level seroprevalence were seropositive to the ELISA. Karangasem had the highest test prevalence at 97.3% (95% CI: 93.1-99.2) while Badung had a slightly lower prevalence at 96.6% (95% CI: 92.2-98.9), and Denpasar had the lowest prevalence at 96% (95% CI: 91.5-98.5) (p=0.84). In herd-level seroprevalence, all sampled herds contained one or more seropositive pigs (overall herd-level seroprevalence 100% [95% CI: 97.7-100]). No animal-level factors were significantly associated with seropositivity (all p values >0.05). For the herd-level risk factors relating to pig management and husbandry practices adopted, no analysis model could be generated, as all the sampled herds were seropositive. More than 90% seroprevalence detected in this study indicates high natural JEV infection occurred in pigs, which highlights the high public health risk of the infection in the areas.

Greater physical fitness (Vo2Max) in healthy older adults associated with increased integrity of the Locus Coeruleus-Noradrenergic system.

Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo2max - a measure of oxygen uptake and physical fitness (PF). In the current study, we hypothesised that greater Vo2 max would be related to greater Locus Coeruleus (LC) MRI signal intensity. As hypothesised, greater Vo2max related to greater LC signal intensity across 41 healthy adults (age range 60-72). As a control procedure, in which these analyses were repeated for the other neuromodulators' seeds (for Serotonin, Dopamine and Acetylcholine), weaker associations emerged. This newly established link between Vo2max and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the noradrenergic system as a possible key factor building Reserve, it also provide grounds for increasing LC-NA system resilience to neurodegeneration via Vo2max enhancement.

Efficient free-space to on-chip coupling of THz-bandwidth pulses for biomolecule fingerprint sensing.

Wide bandwidth THz pulses can be used to record the distinctive spectral fingerprints related to the vibrational or rotational modes of polycrystalline biomolecules, and can be used to resolve the time-dependent dynamics of such systems. Waveguides, owing to their tight spatial confinement of the electromagnetic fields and the longer interaction distance, are promising platforms with which to study small volumes of such systems. The efficient input of sub-ps THz pulses into waveguides is challenging owing to the wide bandwidth of the THz signal. Here, we propose a sensing chip comprised of a pair of back-to-back Vivaldi antennas feeding into, and out from, a 90° bent slotline waveguide to overcome this problem. The effective operating bandwidth of the sensing chip ranges from 0.2 to 1.15 THz, and the free-space to on-chip coupling efficiency is as high as 51% at 0.44 THz. Over the entire band, the THz signal is ∼42 dB above the noise level at room temperature, with a peak of ∼73 dB above the noise. In order to demonstrate the use of the chip, we have measured the characteristic fingerprint of α-lactose monohydrate, and its sharp absorption peak at ∼0.53 THz was successfully observed, demonstrating the promise of our technique. The chip has the merits of efficient in-plane coupling, ultra-wide bandwidth, ease-of-integration, and simple fabrication. It has the potential for large-scale manufacture, and can be a strong candidate for integration into other THz light-matter interaction platforms.

Anifrolumab in systemic lupus erythematosus.

Systemic lupus erythematosus is a complex autoimmune disease with variable disease presentation and progression. Hydroxychloroquine and corticosteroids are first-line therapies. Disease severity and organ system involvement guide escalation of immunomodulatory medications beyond these mainstays. Anifrolumab is a first-in-class global type 1 interferon inhibitor recently approved by the United States Food and Drug Administration (FDA) for systemic lupus erythematosus in addition to standard of care. This article reviews the role of type 1 interferons in lupus pathophysiology and the evidence leading to anifrolumab's approval with particular emphasis on the MUSE, TULIP-1 and TULIP-2 trials. In addition to standard of care, anifrolumab can reduce corticosteroid requirements and reduce lupus disease activity, especially skin and musculoskeletal manifestations, with an acceptable safety profile.

An outbreak of tuberculosis in endangered northern pig-tailed macaques (Macaca leonina) and milu deer (Elaphurus davidianus) from a zoo in China.

BACKGROUND: Tuberculosis (TB) is a zoonotic disease that affects humans and domesticated and wild animals. Animals in zoos are potentially an important source of TB for humans; however they are often neglected in routine disease surveillance programs. This investigation reports an outbreak of TB in milu deer and northern pig-tailed macaques in a zoo in Wuhan, China, which highlighted the need for improved prevention and control of TB in China. METHODS: Between 24 November and 9 December 2020 two milu deer and a northern pig-tailed macaque that were displaying signs of wasting died. Post-mortem, histopathological diagnosis and acid fast staining were used for the dead animals. Multiple PCR for Mycobacterium tuberculosis complex (MTBC) was performed to identify the bacterial in both milu deer and northern pig-tailed macaque. The serum antibody iELISA for MTBC was then performed for all the surviving milu deer and northern pig-tailed macaques. Six seropositive milu deer and a seropositive northern pig-tailed macaque were subsequently euthanised and, along with two other dead milu deer, necropsied. DNA from these tissue samples was extracted and detected MTBC using PCR and Real-time PCR. Subsequently bacterial isolation was used to confirm the infection. RESULTS: The lungs of the dead animals displayed gross and histological TB-like lesions and changes, and red staining bacilli were detected in smears of the lesions by microscopy after acid fast staining. Mycobacterium bovis (M. bovis) was detected in the two milu deer and Mycobacterium tuberculosis (M. tb) in the northern pig-tailed macaque using multiple PCR for MTBC. 35.3% surviving milu deer and 50% surviving northern pig-tailed macaques MTBC serologically positive. Six of the euthanised milu deer were also positive on a DNA test for M. bovis and the euthanised northern pig-tailed macaque was positive to M. tb. CONCLUSIONS: This is the first report of tuberculosis in the endangered species, milu deer and northern pig-tailed macaques, in China, and warrants urgent attention by researchers and conservation authorities. These cases highlight the need for expanding surveillance for MTBC to zoos in China.

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.